A high field NMR spectrometer is needed to support ongoing studies of biomolecular structure at the University of Texas Health Science Center at San Antonio. If funded, the proposed spectrometer will be dedicated to biological-oriented research that requires state-of-the-art high-field NMR instrumentation and relatively long, continuous blocks of instrument time. The proposed instrument will greatly enhance the research of seven major users. Common features of this diverse group of users include: 1) An immediate need for on site high-field biomolecular NMR instrumentation, 2) Research problems dedicated towards solving fundamental problems in contemporary biochemistry, and 3) NIH or NSF supported research programs, having a significant NMR component. Research in the following diverse areas will be significantly advanced by the proposed instrument: (1) Cytokine-cytokine research and Protein- RNA interactions (Hinck), (2) The effects of amino acid substitutions on the structure, stability, and folding pathways of cytochrome c (Nall), (3) The role of PDZ domains in mediating protein localization (Masters), (4) Flexibility and function in the apical domain of the chaperonin GroEL (Horowitz), (5) Substrate specificities and mechanism of the mutT family of phosphohydrolases (Barnes), (6) Cytochrome exidase-cytochrome c interactions as probed by H-D functional labeling (Robinson), and (7) Core histone tail domain interactions (Hansen). The request is justified by the urgent need for high field NMR instrumentation in San Antonio with the ability to perform triple resonance and pulsed field gradient experiments that are essential to the data collection needs of our user base. The proposed instrument has the strong endorsement of the University. The requested funds of $400,000 will be combined with $454,000 from sources within the University of Texas Health Sciences Center at San Antonio. The University will also provide the resources to cover instrument installation, maintenance, and the salary for the NMR facility manager. The instrument will become a core component of the Institutions Center for Biomolecular Structure Analysis, a comprehensive center for macromolecular structure determination, which occupies over 11,000 ft2 of newly completed research space in the Allied Health Sciences Building on the University of Texas Health Science Center at San Antonio campus. The instrument will operate as a shared resource serving the University of Texas Health Science Center at San Antonio and the South Texas research community.